Healthcare utilization and expenditures in patients with tricuspid regurgitation: A population-based cohort study

Highlights • Most cases of tricuspid regurgitation are not associated with heart failure.• Tricuspid regurgitation patients associated with heart failure were older, sicker, and sought medical attention more frequently than those with no heart failure and inconclusive heart failure.• Clinical significant tricuspid regurgitation patients are more likely to be hospitalized, use more healthcare resources, and face higher financial burdens.


Introduction
Tricuspid regurgitation (TR) is one of the most common valvular heart diseases, with over 80 % of cases diagnosed during a routine echocardiogram [1].A study conducted in 2006 in the United States estimated that 1.6 million people suffer from moderate to severe TR [2].The pathophysiology of TR involves the failure of the TV leaflets to coapt properly, which leads to backflow of blood.This backflow increases the volume load on the right atrium and right ventricle,which eventually leads to right heart failure if untreated.The primary etiological factors include conditions like rheumatic heart disease, infective endocarditis, and carcinoid syndrome, while secondary TR is often due to left-sided heart diseases, pulmonary hypertension, or atrial fibrillation [3][4][5].
Therapeutic strategies for TR depend on the severity and underlying cause of the regurgitation.Medical management has traditionally been the first-line treatment for primary TR, while secondary TR is treated based on the underlying cause [6].Medical management typically includes the diuretics use manage symptoms of congestion and aldosterone antagonists to counter secondary hyperaldosteronism [7].Treating the underlying condition is crucial in secondary TR.Surgical options like annuloplasty, valve repair, or valve replacement are considered when medical therapy is insufficient [8].Annuloplasty, which involves suturing the TV annulus to a prosthetic ring, is often performed in cases of annular dilation [9].Valve repair or replacement is indicated for primary valve abnormalities or when annuloplasty is not feasible [10].
This study assesses the incidence of TR in a nationwide sample of patients treated in Taiwan to provide context for the occurrence and management of TR, along with the healthcare utilization and expenditures of patients with varying severities of TR.

Data source and patient definition
The data for this retrospective, population-based study were Patients with or without clinically significant TR who met the initial criteria above were divided into six mutually exclusive, collectively exhaustive groups based on whether significant TR was present (sTR) or not (nsTR), and whether HF was present (HF) or not present (noHF)(HF was identified as patients with ICD-10 coding I13.0, I13.2 and I50.#) [11], or inconclusive (incHF).The observation period of this study was the 12-month before the first TR diagnosis/invasive therapy and 6month after first TR diagnosis/invasive therapy.HF diagnosis was defined as following: (1) not present HF (noHF): without HF diagnosis in the database during observation period, (2) present HF (HF): with at least one inpatient or two outpatient diagnoses of HF during observation period, and (3) inconclusive HF (incHF): with only one outpatient diagnosis of HF during observation period.Patients were considered to have clinically significant TR (sTR) if they had a history of pulmonary hypertension with ascites, edema, or hepatic insufficiency during the baseline or landmark periods, or if they had undergone TV surgery during that time.

Data analyses
SAS 9.1 (SAS Institute Inc., Cary, NC) was used to conduct data analyses.Variables were identified using the criteria described above.Frequencies or percentages were used to define categorical variables.
Patients in the HF and incHF cohorts were older than those in the noHF cohort, regardless of whether they had clinically significant TR or not.The average age of the nsTR-noHF cohort was 60.57 years, while the nsTR-HF and nsTR-incHF cohorts had average ages of 76.85 years and 76.06 years, respectively.The average age of the sTR-noHF cohort was 68.45 years, while that of the sTR-HF and sTR-incHF cohorts were 72.72 and 76.55 years, respectively.The nsTR-HF cohort had a higher ECI (20.49) than the nsTR-noHF (7.99) or nsTR-incHF cohorts (19.90) (Table 1).The HF cohort had a higher prevalence of almost all underlying diseases than those in the noHF and incHF cohorts (Table 2).The sTR-incHF cohort had a higher ECI score of 26.18 compared to the sTR-noHF (14.32) and sTR-HF cohorts (23.19) (Table 1).Patients with clinically significant TR scored significantly higher on ECI than those without.This was true for all TR patients, regardless of the HF diagnosis.

Healthcare utilization outcomes for patients with TR
Healthcare utilization data for patients with TR were collected at the 12-month baseline and 6-month landmark periods (Table 3).CHF and all-cause emergency department visits, hospitalizations, LOS, and outpatient department (OPD) visits were all calculated.The sTR-HF group had the highest utilization pattern in CHF OPD visits.The sTR-incHF group had the highest utilization patterns in the inpatient department (IPD), LOS, and CHF/all-cause costs.The nsTR-incHF group higher annual healthcare costs (NTD 293,569) than those with nsTR-HF or nsTR-noHF (NTD 276,827 and NTD 66,834, respectively) in patient cohorts without clinically significant TR.In patient cohorts with clinically significant TR, patients with sTR-incHF had higher annual healthcare expenditures (NTD 769,909) than patients with sTR-HF or sTR-noHF (NTD 480,711 and NTD 210,842, respectively).

Regression
Table 4 shows the regression results for each of the annualized interest outcome variables (total expenditures and LOS).The two main independent variables-HF and clinically significant TR-were statistically significant for expenditures and all-cause hospitalizations.A diagnosis of HF increased to NTD 122,119 (p <0.0001) in annualized expenditures and 5.60 days (p = 0.0043) in annualized LOS.Patients with clinically significant TR experienced an increase of NTD 485,014 (p <0.0001) in annualized expenditures and of 5.53 days (p = 0.4347) in annualized LOS.Age was statistically significant in expenditures and allcause hospitalizations, but not in annualized LOS.Annualized expenditures for pulmonary hypertension, ascites, and edema were significantly higher (NTD 394,779, NTD 89,488, and NTD 18,000, respectively; p <0.0001).The ECI score varied significantly for all three outcome variables of interest.

Discussion
This study used Taiwan's NHIRD to analyze epidemiological and healthcare utilization data for TR and sTR patients from 2017 to 2019.TR cases comprised 0.089 % of the total population.In this study, patients with noHF outnumbered HF or incHF patients by a large margin.There were more patients with sTR-noHF than those with sTR-HF or sTR-incHF.Additionally, we looked at the healthcare utilization and annual expenditures of with or without clinically significant TR patients.Compared to the HF and noHF cohorts, the incHF cohort had higher healthcare utilization and annual expenditures; this was due to incHF patients' high ECI scores and comorbidities.The noHF cohort had fewer comorbidities and lower healthcare utilization in comparison to the HF and incHF cohorts.
Despite the low prevalence of significant TR in the general population (~0.5 % of patients who undergo echocardiographic testing), CHF and other valvular heart diseases are commonly associated with significant TR [13].In another retrospective study, 23 % of patients with symptomatic HF had moderate to severe TR [14].Among all patients with TR, the prevalence of clinically significant TR in our study (sTR-noHF=504, sTR-HF=155, and sTR-incHF=11) was 3.18 %, while the percentage of clinically significant TR among HF patients was 19.00 % (sTR-HF=155).These findings were consistent with those from previous studies [13,14].
Several observational studies have found that patients with clinically significant TR and CHF have a longer LOS, more rehospitalizations, and higher mortality rates [13][14][15][16].Patients with clinically significant TR or HF had more IPD visits and higher medical costs (Table 3).Following the regression analysis, two major independent variables (HF and clinically significant TR) were statistically significant across expenditures and allcause hospitalizations (Table 4).These findings reflect rising rehospitalization rates among patients with HF and clinically significant TR in Western countries and Asia.HF is associated with higher expenditures and all-cause hospitalizations along with longer LOS (Table 4).This indicates that HF is an important factor in the economic burden for patients with TR.
In the current study, the annual medical expenses associated with sTR-HF were 1.59 times greater than those associated with sTR-noHF (Table 3).This result was consistent with other claims database studies, which found a 1.41-or 1.15-fold increase in incremental annual medical expenditures in patients with HF and clinically significant TR [11,17].Compared to these two U.S. claims database studies, the annual LOS in sTR-HF were higher than those in sTR-noHF, and the incremental trend was similar; however, the sTR-HF cohort in the current study was associated with 34.52 days annual LOS, which was significantly higher than 4.31 days (Cork et al., 2020) and 7.1 days (Barker et al., 2021).The reason for this could be the difference in health insurance coverage between Taiwan and the United States.In Taiwan, health insurance covers almost all diseases; patients are only responsible for copayments, the upper limits of which are capped at 7 USD per OPD and 1,433 USD per IPD.Thus, Taiwan's higher rates of outpatient and inpatient service utilization may be attributed to relatively low out-of-pocket expenses.
Although NHIRD data provided useful analyses, this investigation was limited by the database's design.First, we were unable to assess disease severity due to a lack of information on self-payment for medications, laboratory data, and patients' vital statistics (height, weight, etc.) is limited; therefore, we were unable to assess disease severity.Second, because the study design was solely based on the ICD-10-CM and ICD-10-PCs, coding errors, misclassifications, or differences between hospitals and physicians may have influenced our findings.Finally, some TR surgeries or procedures were not reimbursed in Taiwan from 2017 to 2019.The National Health Insurance Administration

Table 1
Demographic data.

Table 2
The underlying diseases among these TR Patients.

Table 3
Economic burden in TR Patients.

Table 4
Regression results in TR Patients.